Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The purpose of this project is to study the mechanisms for immune evasion and latent infection by VZV. We have shown that infection of fibroblasts with VZV results in down-regulation of expression of proteins that are important for recognition by the immune system (MHC class I antigens). While the total amount of these proteins was unchanged in infected cells, the amount of class I antigen expressed on the surface of infected cells was reduced. Since MHC class I proteins are important for the immune system to recognize VZV infected cells, the ability of the virus to reduce their expression provides a mechanism by which the virus might evade the immune system. We have also studied a VZV gene (ORF21) that has been reported to be expressed during latency in humans. During infection of cells in culture, this gene was shown to be up-regulated by VZV infection or by expression of a VZV immediate-early gene (ORF62). The ends of the RNA transcripts that encode VZV ORF21 have been mapped and the region of the gene that regulates its expression (promoter) has been identified.